Light adjustable intraocular lenses with a caged photoinitiator

Abstract

Light Adjustable Lenses are described with a caged photoinitator and advanced polymerization control that greatly suppress unintended optical power drift in these lenses. Some Light Adjustable Lenses comprise a polymer silicone network, molded in the presence of a mobile macromer and an ultraviolet absorber; and a cage-photoinitiator complex; wherein a caged photoinitiator can be freed from a cage by a first photon of a first illumination; the free photoinitiator can be activated by a second photon of a second illumination; and the activated photoinitiator is capable of inducing a polymerization reaction of the mobile macromer, leading to a changing of an optical power of the LAL.

1 . A Light Adjustable Lens (LAL), comprising:
 a polymer silicone network, molded in the presence of a mobile macromer and an ultraviolet absorber; and   a cage-photoinitiator complex; wherein
 a caged photoinitiator can be freed from a cage by a first photon of a first illumination; 
 the free photoinitiator can be activated by a second photon of a second illumination; and 
 the activated photoinitiator is capable of inducing a polymerization reaction of the mobile macromer, leading to a changing of an optical power of the LAL. 
   
     
     
         2 . The LAL of  claim 1 , comprising:
 a front protection layer, including a switchable ultraviolet absorber.   
     
     
         3 . The LAL of  claim 1 , wherein
 the polymerization reaction includes grafting a mobile macromer onto the polymer silicone network, or bonding to another mobile macromer, wherein the bonded macromers eventually entangle with the polymer silicone network.   
     
     
         4 . The LAL of  claim 1 , wherein:
 the photoinitiator is freed from the cage by the first illumination into a mobile state without activation.   
     
     
         5 . The LAL of  claim 1 , wherein:
 the cage-photoinitiator complex has a wavelength-dependent first absorptivity with a first maximum at a first peak wavelength in a range of 250 nm-450 nm; and   the free photoinitiator has a wavelength-dependent second absorptivity with a second maximum at a second peak wavelength in a range of 250 nm-450 nm.   
     
     
         6 . The LAL of  claim 5 , wherein:
 the first peak wavelength and the second peak wavelength are both in a range of 330 nm-380 nm.   
     
     
         7 . The LAL of  claim 5 , wherein:
 a first center wavelength of the first illumination is different from a second center wavelength of the second illumination;   the first center wavelength is selected such that the first absorptivity of the cage-photoinitiator complex is greater than 1% of the first maximum; and   the second center wavelength is selected such that the second absorptivity of the free photoinitiator is greater than 1% of the second maximum.   
     
     
         8 . The LAL of  claim 5 , wherein:
 a first center wavelength of the first illumination is different from a second center wavelength of the second illumination;   the first center wavelength is selected such that the first absorptivity of the cage-photoinitiator complex is in a range of 50-2,000 L/(mol cm); and   the second center wavelength is selected such that the second absorptivity of the free photoinitiator is in a range of 50-2,000 L/(mol cm).   
     
     
         9 . The LAL of  claim 5 , wherein:
 the first illumination and the second illumination are generated by the same illumination source with a common center wavelength.   
     
     
         10 . The LAL of  claim 9 , wherein:
 the common center wavelength is selected such that   the first absorptivity of the cage-photoinitiator complex at the common center wavelength is at least 0.1% of the first maximum; and   the second absorptivity of the free photoinitiator at the common center wavelength is at least 0.1% of the second maximum.   
     
     
         11 . The LAL of  claim 9 , wherein:
 the common center wavelength is selected such that   the first absorptivity of the cage-photoinitiator complex at the common center wavelength is in a range of 10-5,000 L/(mol cm); and   the second absorptivity of the free photoinitiator at the common center wavelength is in a range of 10-5,000 L/(mol cm).   
     
     
         12 . The LAL of  claim 5 , wherein:
 the first peak wavelength is shorter than the second peak wavelength.   
     
     
         13 . The LAL of  claim 5 , wherein:
 the first maximum absorptivity of the cage-photoinitiator complex is greater than the second absorptivity maximum of the free photoinitiator.   
     
     
         14 . The LAL of  claim 5 , wherein:
 the first maximum absorptivity of the cage-photoinitiator complex is smaller than the second absorptivity maximum of the free photoinitiator.   
     
     
         15 . The LAL of  claim 1 , wherein
 the free photoinitiator is Norrish type I, and thereby, after getting activated by the second illumination, the activated photoinitiator is capable of directly inducing the polymerization reaction of the mobile macromer.   
     
     
         16 . The LAL of  claim 1 , wherein
 the free photoinitiator is Norrish type II, and thereby, after getting activated by the second illumination, the activated photoinitiator is capable of inducing the polymerization reaction of the mobile macromer via activating one of a contributory initiator, a sacrificial hydrogen donor, another free photoinitiator, or itself by an intramolecular reaction; wherein   the activation involves the free photoinitiator acquiring a hydrogen.   
     
     
         17 . The LAL of  claim 16 , wherein:
 the contributory initiator is one of an alcohol, an amine, or a hydrosilane that contained the acquired hydrogen in a labile bond.   
     
     
         18 . The LAL of  claim 1 , wherein:
 the free photoinitiator is hydrophilic and thereby has an elution time in which at least 80% of the free photoinitiator elutes out of the LAL into an eye after implantation of the LAL into the eye and after the freeing of the caged photoinitiator by the first illumination; wherein   the elution time is in a range of 1 minute-1 month.   
     
     
         19 . The LAL of  claim 18 , wherein:
 the elution time is in a range of 10 minutes-1 week.   
     
     
         20 . The LAL of  claim 18 , wherein:
 when the second illumination is characterized by the solar spectrum with an intensity less than 10 mW/cm 2  in the wavelength range shorter than 400 nm, then the second illumination initiates the polymerization in an initiation time that is longer than the elution time of the free photoinitiator; and   when the second center wavelength of the second illumination is in a range of 300-400 nm with an average intensity greater than 30 mW/cm 2 , then the second illumination initiates the polymerization in an initiation time that is shorter than the elution time of the free photoinitiator;   wherein the initiation time is a time in which the second illumination activates the free photoinitiator that thereby initiates the polymerization reaction with at least a 10% polymerization rate.   
     
     
         21 . The LAL of  claim 1 , wherein:
 when the first and the second illumination are characterized by the solar spectrum with an intensity less than 10 mW/cm 2  in the wavelength range shorter than 400 nm, then these illuminations initiate the polymerization in an initiation time that is longer than a dissociation time of the free photoinitiator; and   when the first center wavelength of the first illumination and the second center wavelength of the second illumination are in a range of 300-400 nm range with an average intensity greater than 30 mW/cm 2 , then these illuminations initiate the polymerization in an initiation time that is shorter than the dissociation time of the free photoinitiator; wherein   the free photoinitiator is thermally unstable, and thereby has the dissociation time in which at least 80% of the free photoinitiator dissociates after implantation of the LAL into the eye;   the initiation time is a time in which the free photoinitiator absorbs a photon and initiates the polymerization reaction with at least a 10% polymerization rate; and   the dissociation time is in a range of 1 minute-1 month.   
     
     
         22 . The LAL of  claim 1 , wherein:
 the cage-photoinitiator complex is 5-hydroxy-2,2-diphenyl-4H-benzo-[1,3]dioxinone (a.k.a. caged benzophenone (BP)):   
       
         
           
           
               
               
           
         
         and the free photoinitiator is benzophenone (BP): 
       
       
         
           
           
               
               
           
         
       
     
     
         23 . The LAL of  claim 1 , wherein:
 the cage-photoinitiator complex is 2-(benzo-[1,3]dioxolyl)-5-hydroxy-2-phenyl-4H-benzo[d][1,3]dioxinone (a.k.a. caged phenyl benzodioxole (PBD)):   
       
         
           
           
               
               
           
         
         and the free photoinitiator is benzo[d][1,3]dioxolyl (phenyl) methanone (a.k.a. phenyl benzodioxole (PBD)): 
       
       
         
           
           
               
               
           
         
       
     
     
         24 . The LAL of  claim 1 , wherein:
 the cage-photoinitiator complex is 5-hydroxy-2-(naphthalenyl)-2 phenyl-4H-benzo-dioxinone (a.k.a. caged NPM)   
       
         
           
           
               
               
           
         
       
       and the free photoinitiator is 2-naphthalenyl phenylmethanone (a.k.a. NPM): 
       
         
           
           
               
               
           
         
       
     
     
         25 . The LAL of  claim 1 , wherein:
 the cage-photoinitiator complex is caged 9-anthracenyl (phenyl) methanone (a.k.a. caged APM):   
       
         
           
           
               
               
           
         
         and the free photoinitiator is 9-anthracenyl (phenyl) methanone (a.k.a. APM): 
       
       
         
           
           
               
               
           
         
       
     
     
         26 . The LAL of  claim 1 , wherein:
 the cage-photoinitiator complex is 2-(4-(diphenylamino)phenyl)-5-hydroxy-2-phenyl-4H-benzo[d][1.3]dioxinone (a.k.a. caged DPABP):   
       
         
           
           
               
               
           
         
         and the free photoinitiator is 4-diphenylamino benzophenone (a.k.a. DPABP):